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PXD039041

PXD039041 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleOvol2 sustains postnatal thymic epithelial cell identity
DescriptionThymic epithelial cells (TECs) begin to develop embryonically in mice and humans, expand in number through puberty, and then stabilize before declining during early adulthood. We identified a mechanism by which TEC numbers and function are maintained postnatally, discovered through a forward genetic screen for altered immune cell development in mice. A viable missense allele (C120Y) of Ovol2 resulted in lymphopenia, in which T cell development was compromised by loss of medullary TECs and dysfunction of cortical TECs. OVOL2 is an essential regulator of epithelial to mesenchymal transition (EMT), and we show that the epithelial identity of TECs is subverted towards a mesenchymal state in OVOL2-deficient mice. We document global changes in chromatin accessibility correlated with gene expression, particularly affecting genes involved in epithelial and mesenchymal cell proliferation and differentiation. OVOL2 regulates chromatin accessibility by inhibiting the BRAF-HDAC complex. In particular, it disrupts the RCOR1-LSD1 complex by directly binding to the lysine demethylase LSD1, resulting in inhibition of LSD1-mediated H3K4me2 demethylation. Thus, OVOL2 controls the epigenetic landscape of TECs, preventing EMT and enforcing TEC identity to support T cell development in the thymus.
HostingRepositoryMassIVE
AnnounceDate2023-10-24
AnnouncementXMLSubmission_2023-10-24_09:48:30.402.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJames Moresco
SpeciesList scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF; Orbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-12-21 09:13:01ID requested
12023-10-24 09:48:30announced
Publication List
no publication
Keyword List
submitter keyword: OVOL2, TECs, thymus, LSD1/RCOR1 complex
Contact List
Jin Huk Choi
contact affiliationUniversity of Texas Southwestern Medical Center
contact emailJin.Choi@utsouthwestern.edu
lab head
James Moresco
contact affiliationUT Southwestern
contact emailjames.moresco@utsouthwestern.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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